4-methoxy-5,6,7,8-tetrahydronaphthoic acid | 854590-36-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-methoxy-5,6,7,8-tetrahydronaphthoic acid
• 英文别名: 4-methoxy-5,6,7,8-tetrahydro-[1]naphthoic acid；4-Methoxy-5,6,7,8-tetrahydro-[1]naphthoesaeure；4-Methoxy-5,6,7,8-tetrahydro-naphthalen-1-carboxylic Acid；4-Methoxy-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid
• CAS: 854590-36-6
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: UJQHGNOJZRJDNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methoxy-5,6,7,8-tetrahydronaphthoic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 20.0h， 生成 N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-4-methoxy-5,6,7,8-tetrahydronaphthalene-1-carboxamide
  参考文献：
  名称：

  2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists

  摘要：

  Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pK(i) values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pK(i) 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 mug/kg iv), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.

  DOI：

  10.1021/jm00070a008
• 作为产物：
  描述：

  1-(8-methoxytetralin-5-yl)ethanone 在 氢氧化钾 、 potassium hypochlorite 、 potassium carbonate 、 sodium sulfite 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 以100%的产率得到4-methoxy-5,6,7,8-tetrahydronaphthoic acid
  参考文献：
  名称：

  Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds

  摘要：

  本发明涉及1,4-二取代萘骨架化合物及其他密切相关的骨架化合物。本发明还涉及这些化合物的组合式库。此外，本发明涉及一种鉴定蛋白质-蛋白质相互作用拮抗剂的方法。该方法首先涉及提供本文描述的化合物。接下来，将该化合物与蛋白质-蛋白质相互作用目标复合物的相互作用蛋白质接触，使该化合物能够与相互作用蛋白质竞争。然后，测量该化合物抑制蛋白质-蛋白质相互作用目标复合物形成的活性。最后，确定抑制蛋白质-蛋白质相互作用目标复合物形成的化合物为蛋白质-蛋白质相互作用拮抗剂。还公开了一种调节蛋白质-蛋白质相互作用的方法。该方法涉及将本文描述的化合物与蛋白质-蛋白质相互作用目标的相互作用蛋白质接触，从而调节相互作用蛋白质之间的蛋白质-蛋白质相互作用。

  公开号：

  US20050153366A1

文献信息

• A Study of the Haloform Reaction
  作者：Richard T. Arnold、Robert Buckles、Janet Stoltenberg

  DOI：10.1021/ja01230a015

  日期：1944.2
• US7662750B2
  申请人：——

  公开号：US7662750B2

  公开（公告）日：2010-02-16
• [EN] PROTEIN-PROTEIN INTERACTION ANTAGONIST SCREENING LIBRARIES BASED UPON 1,4-DISUBSTITUTED NAPHTHALENES AND RELATED SCAFFOLDS<br/>[FR] BANQUES DE CRIBLAGE D'ANTAGONISTES DE L'INTERACTION PROTEINE-PROTEINE A BASE DE NAPHTALENES 1,4-DISUBSTITUES ET STRUCTURES D'ECHAFAUDAGE ASSOCIEES
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2005057171A2

  公开（公告）日：2005-06-23

  The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.
• 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists
  作者：Robin D. Clark、Aaron B. Miller、Jacob Berger、David B. Repke、Klaus K. Weinhardt、Bruce A. Kowalczyk、Richard M. Eglen、Douglas W. Bonhaus、Chi Ho Lee

  DOI：10.1021/jm00070a008

  日期：1993.9

  Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pK(i) values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pK(i) 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 mug/kg iv), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.
• Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds
  申请人：Hangauer G. David

  公开号：US20050153366A1

  公开（公告）日：2005-07-14

  The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.

  本发明涉及1,4-二取代萘骨架化合物及其他密切相关的骨架化合物。本发明还涉及这些化合物的组合式库。此外，本发明涉及一种鉴定蛋白质-蛋白质相互作用拮抗剂的方法。该方法首先涉及提供本文描述的化合物。接下来，将该化合物与蛋白质-蛋白质相互作用目标复合物的相互作用蛋白质接触，使该化合物能够与相互作用蛋白质竞争。然后，测量该化合物抑制蛋白质-蛋白质相互作用目标复合物形成的活性。最后，确定抑制蛋白质-蛋白质相互作用目标复合物形成的化合物为蛋白质-蛋白质相互作用拮抗剂。还公开了一种调节蛋白质-蛋白质相互作用的方法。该方法涉及将本文描述的化合物与蛋白质-蛋白质相互作用目标的相互作用蛋白质接触，从而调节相互作用蛋白质之间的蛋白质-蛋白质相互作用。